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壳三糖 III-ia 与壳聚糖物理相互作用的特性。构建壳三糖 III-ia 药物传递系统。

Characterization of physical interaction between Casiopeina III-ia and chitosan. Toward a Cas III-ia drug delivery system.

机构信息

Depto. Farmacia, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, México DF 04510, Mexico.

出版信息

Carbohydr Res. 2011 Jan 3;346(1):121-6. doi: 10.1016/j.carres.2010.07.007. Epub 2010 Nov 17.

Abstract

Casiopeínas are a new generation of anticancer drugs that have shown great in vitro and in vivo antineoplastic activities. Information about interaction drug-excipient, for developing a based-nanoparticle drug delivery system, has not been investigated yet. In order to elucidate if chitosan (CS) modifies the copper complex due to its interaction with Cu(2+) ion, different studies in aqueous media between CS and Casiopeina III-ia (Cas III-ia) were carried out. CS-Cas III-ia mixtures were characterized by viscosity curves, UV-vis, EPR, and in vivo activity against HeLa cell line. Rheological behavior showed a decrease of viscosity when the drug was present due to diminished electrostatic interactions of charged amine group. UV-vis results illustrate that Cas III-ia is not stable at low pH as a result of interaction with acetic acid. However, when chitosan is present at the acidic solution Cas III-ia is stable. These results are supported by EPR studies. Finally, activity of the drug against HeLa cell line was not modified. Therefore, the present work presents evidence that there is no breaking of copper complex due to interaction between CS and Cas III-ia in acidic media. In addition, Cas III-ia maintains both its stability and effectiveness against cancer cell line.

摘要

金丝桃素是新一代抗癌药物,已显示出强大的体外和体内抗肿瘤活性。关于药物-赋形剂相互作用的信息,尚未用于开发基于纳米粒子的药物传递系统。为了阐明壳聚糖(CS)是否由于与 Cu(2+) 离子的相互作用而改变铜配合物,在水介质中进行了 CS 和金丝桃素 III-ia(Cas III-ia)之间的不同研究。通过粘度曲线、UV-vis、EPR 和对 HeLa 细胞系的体内活性对 CS-Cas III-ia 混合物进行了表征。流变行为表明,由于带电荷的氨基的静电相互作用减弱,当存在药物时,粘度降低。UV-vis 结果表明,由于与醋酸的相互作用,Cas III-ia 在低 pH 值下不稳定。然而,当壳聚糖存在于酸性溶液中时,Cas III-ia 是稳定的。这些结果得到了 EPR 研究的支持。最后,药物对 HeLa 细胞系的活性没有改变。因此,本工作证明,在酸性介质中,CS 与 Cas III-ia 之间的相互作用不会破坏铜配合物。此外,Cas III-ia 保持其稳定性和对癌细胞系的有效性。

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